Study to Evaluate Effects of Emixustat Hydrochloride in Subjects With Proliferative Diabetic Retinopathy

• Sponsor: Kubota Vision Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02753400
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Actual Duration (Months): 19
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

To evaluate the effects of oral emixustat hydrochloride (emixustat) on aqueous humor biomarkers associated with proliferative diabetic retinopathy (PDR) from baseline to week 12.

Condition or Disease	Intervention/Treatment	Phase
Proliferative Diabetic Retinopathy	Drug: emixustat hydrochloride; Other: Placebo	Phase 2

Detailed Description

This is a multicenter, randomized, double-masked, placebo-controlled study to evaluate the effects of emixustat in subjects with PDR. Subjects will be randomly assigned to either emixustat or placebo arms and treated once daily (QD) for 12 weeks. Doses of emixustat will be doubled on a weekly basis until week 4 after which all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen. Subjects in the placebo group will be mock-titrated on the same schedule as those in the emixustat arm.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Masked, Placebo-Controlled, Pilot Study to Evaluate Effects of Emixustat Hydrochloride on Aqueous Humor Biomarkers Associated With Proliferative Diabetic Retinopathy
• Actual Study Start Date: May 1, 2016
• Actual Primary Completion Date: Nov 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Emixustat hydrochloride Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A) Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B) Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C) Week 4- Four emixustat HCl tablets (Strength C) All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen.	Drug: emixustat hydrochloride; Tablet for oral administration; Other Names: ACU-4429, Emixustat HCl ; Other: Placebo; Placebo tablets for oral administration contain only inactive ingredients
Placebo Comparator: Placebo Four placebo tablets are administered orally once daily for 12 weeks; Subjects in the placebo group will be mock-titrated on the same schedule as those in the active arm.	Other: Placebo; Placebo tablets for oral administration contain only inactive ingredients

Outcome Measures

Primary Outcome Measures

1. Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values [Baseline and 12 weeks]

   All values for IL-1β were below the lower limit of detection and were recorded as zero. Tests for IP-10 and MCP-1 failed accuracy and stability testing during assay development and were dropped from the study. The assay for PDGF-AA could not be developed.and results were not reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Able and willing to provide written informed consent

• Documented diagnosis of type 1 or type 2 diabetes mellitus

• Meets specific ocular criteria for the study eye including but not limited to, the presence of PDR with or without diabetic macular edema in study eye for which treatment can be deferred for at least 4 weeks after Day 1 visit

• Media clarity, pupillary dilation, and subject cooperation sufficient to obtain adequate assessments

Exclusion Criteria:

• Any condition that would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease or glycemic control)

• History of myocardial infarction or other acute cardiac event

• History of chronic renal failure requiring dialysis or kidney transplant

• Prior participation in any clinical study of emixustat

• Treatment with any investigational study drug within 30 days of screening

• Known allergy to fluorescein sodium for injection in angiography

• Treatment with specific prohibited medications or therapy beginning 4 weeks prior to screening and throughout the duration of the study

• History of systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization

• Pre-specified laboratory abnormalities at screening

• Specific ocular characteristics in the study eye

• Male subjects who are not surgically sterile and are not willing to practice a medically accepted method of birth control with their female partner of childbearing potential from screening through 30 days following completion of the study

• Female subjects of childbearing potential who are not willing to practice a medically accepted method of birth control with their non-surgically sterile male sexual partner from screening through 30 days following completion of the study

• Female subjects who are pregnant or lactating

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retina Institute of California	Arcadia	California	United States

Sponsors and Collaborators

• Kubota Vision Inc.

Investigators

• Study Director: Responsible Medical Officer, Kubota Vision Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 5, 2016

More Information

Publications

None provided.

• Responsible Party: Kubota Vision Inc.
• ClinicalTrials.gov Identifier: NCT02753400
• Other Study ID Numbers: 4429-203
• First Posted: Apr 27, 2016
• Last Update Posted: May 19, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Retinal Diseases; Diabetic Retinopathy

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled from May 2016 through July 2017 at 8 sites in the United States

Arm/Group Title	Emixustat Hydrochloride	Placebo
Arm/Group Description	Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A) Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B) Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C) Week 4- Four emixustat HCl tablets (Strength C) All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen. emixustat hydrochloride: Tablet for oral administration Placebo: Placebo tablets for oral administration contain only inactive ingredients	Four placebo tablets are administered orally once daily for 12 weeks; Subjects in the placebo group will be mock-titrated on the same schedule as those in the active arm. Placebo: Placebo tablets for oral administration contain only inactive ingredients
Period Title: Overall Study
STARTED	12	12
COMPLETED	7	11
NOT COMPLETED	5	1

Baseline Characteristics

Arm/Group Title	Emixustat Hydrochloride	Placebo	Total
Arm/Group Description	Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A) Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B) Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C) Week 4- Four emixustat HCl tablets (Strength C) All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen. emixustat hydrochloride: Tablet for oral administration Placebo: Placebo tablets for oral administration contain only inactive ingredients	Four placebo tablets are administered orally once daily for 12 weeks; Subjects in the placebo group will be mock-titrated on the same schedule as those in the active arm. Placebo: Placebo tablets for oral administration contain only inactive ingredients	Total of all reporting groups
Overall Participants	12	12	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.1 (7.06)	47.4 (11.29)	49.8 (9.52)
Sex: Female, Male (Count of Participants)
Female	7 58.3%	5 41.7%	12 50%
Male	5 41.7%	7 58.3%	12 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 83.3%	6 50%	16 66.7%
Not Hispanic or Latino	2 16.7%	6 50%	8 33.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 8.3%	2 16.7%	3 12.5%
White	11 91.7%	10 83.3%	21 87.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values
Description	All values for IL-1β were below the lower limit of detection and were recorded as zero. Tests for IP-10 and MCP-1 failed accuracy and stability testing during assay development and were dropped from the study. The assay for PDGF-AA could not be developed.and results were not reported.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Not all subjects had primary endpoint end-of-treatment data.

Arm/Group Title	Emixustat Hydrochloride	Placebo
Arm/Group Description	Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A) Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B) Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C) Week 4- Four emixustat HCl tablets (Strength C) All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen. emixustat hydrochloride: Tablet for oral administration Placebo: Placebo tablets for oral administration contain only inactive ingredients	Four placebo tablets are administered orally once daily for 12 weeks; Subjects in the placebo group will be mock-titrated on the same schedule as those in the active arm. Placebo: Placebo tablets for oral administration contain only inactive ingredients
Measure Participants	12	11
IL-6, change from baseline	45.6 (137.1)	4.9 (12.6)
IL-8, change from baseline	4.2 (5.1)	2.6 (4.6)
TGFβ-1, change from baseline	-19.9 (32.4)	-17.5 (43.7)
VEGF, change from baseline	-38.0 (115.1)	-24.8 (277.2)

Adverse Events

Time Frame	Day 115
Arm/Group Title	Emixustat Hydrochloride		Placebo
Arm/Group Description	Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A) Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B) Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C) Week 4- Four emixustat HCl tablets (Strength C) All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen. emixustat hydrochloride: Tablet for oral administration Placebo: Placebo tablets for oral administration contain only inactive ingredients		Four placebo tablets are administered orally once daily for 12 weeks; Subjects in the placebo group will be mock-titrated on the same schedule as those in the active arm. Placebo: Placebo tablets for oral administration contain only inactive ingredients
All Cause Mortality
	Emixustat Hydrochloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)
Serious Adverse Events
	Emixustat Hydrochloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		2/11 (18.2%)
Infections and infestations
Cellulitis	0/12 (0%)	0	1/11 (9.1%)	1
Investigations
Blood potassium increased	0/12 (0%)	0	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Emixustat Hydrochloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/12 (100%)		9/11 (81.8%)
Eye disorders
DELAYED DARK ADAPTATION	9/12 (75%)		1/11 (9.1%)
BLINDNESS DAY	4/12 (33.3%)		3/11 (27.3%)
VISION BLURRED	1/12 (8.3%)		6/11 (54.5%)
VISUAL IMPAIRMENT	6/12 (50%)		1/11 (9.1%)
VITREOUS FLOATERS	4/12 (33.3%)		2/11 (18.2%)
VISUAL ACUITY REDUCED	4/12 (33.3%)		1/11 (9.1%)
CHROMATOPSIA	4/12 (33.3%)		0/11 (0%)
VITREOUS HAEMORRHAGE	3/12 (25%)		1/11 (9.1%)
DIABETIC RETINAL OEDEMA	1/12 (8.3%)		2/11 (18.2%)
ERYTHROPSIA	3/12 (25%)		0/11 (0%)
PHOTOPHOBIA	1/12 (8.3%)		2/11 (18.2%)
RETINAL NEOVASCULARISATION	1/12 (8.3%)		2/11 (18.2%)
RETINAL ANEURYSM	2/12 (16.7%)		0/11 (0%)
RETINAL DETACHMENT	2/12 (16.7%)		0/11 (0%)
RETINAL EXUDATES	0/12 (0%)		2/11 (18.2%)
RETINAL HAEMORRHAGE	1/12 (8.3%)		1/11 (9.1%)
VITREOUS DETACHMENT	2/12 (16.7%)		0/11 (0%)
CATARACT	0/12 (0%)		1/11 (9.1%)
CATARACT CORTICAL	1/12 (8.3%)		0/11 (0%)
DIABETIC RETINOPATHY	0/12 (0%)		1/11 (9.1%)
EYE IRRITATION	0/12 (0%)		1/11 (9.1%)
EYE PAIN	0/12 (0%)		1/11 (9.1%)
EYE PRURITUS	0/12 (0%)		1/11 (9.1%)
FOREIGN BODY SENSATION IN EYES	0/12 (0%)		1/11 (9.1%)
MACULAR FIBROSIS	0/12 (0%)		1/11 (9.1%)
NIGHT BLINDNESS	1/12 (8.3%)		0/11 (0%)
PUNCTATE KERATITIS	0/12 (0%)		1/11 (9.1%)
RETINAL CYST	0/12 (0%)		1/11 (9.1%)
VISUAL BRIGHTNESS	0/12 (0%)		1/11 (9.1%)
VITREOUS ADHESIONS	0/12 (0%)		1/11 (9.1%)
XANTHOPSIA	1/12 (8.3%)		0/11 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN	0/12 (0%)		1/11 (9.1%)
NAUSEA	0/12 (0%)		1/11 (9.1%)
VOMITING	0/12 (0%)		1/11 (9.1%)
General disorders
FATIGUE	0/12 (0%)		1/11 (9.1%)
OEDEMA PERIPHERAL	1/12 (8.3%)		0/11 (0%)
Infections and infestations
CELLULITIS	0/12 (0%)		1/11 (9.1%)
LOWER RESPIRATORY TRACT INFECTION	0/12 (0%)		1/11 (9.1%)
NASOPHARYNGITIS	1/12 (8.3%)		0/11 (0%)
PNEUMONIA	0/12 (0%)		1/11 (9.1%)
SINUSITIS	0/12 (0%)		1/11 (9.1%)
URINARY TRACT INFECTION	0/12 (0%)		1/11 (9.1%)
Injury, poisoning and procedural complications
PROCEDURAL PAIN	0/12 (0%)		1/11 (9.1%)
SKIN ABRASION	1/12 (8.3%)		0/11 (0%)
Investigations
VISUAL ACUITY TESTS ABNORMAL	2/12 (16.7%)		2/11 (18.2%)
BLOOD GLUCOSE INCREASED	1/12 (8.3%)		0/11 (0%)
BLOOD POTASSIUM INCREASED	1/12 (8.3%)		0/11 (0%)
HAEMATOCRIT DECREASED	1/12 (8.3%)		0/11 (0%)
HAEMOGLOBIN DECREASED	1/12 (8.3%)		0/11 (0%)
WEIGHT INCREASED	1/12 (8.3%)		0/11 (0%)
Metabolism and nutrition disorders
DIABETES MELLITUS	1/12 (8.3%)		0/11 (0%)
FLUID RETENTION	1/12 (8.3%)		0/11 (0%)
HYPERKALAEMIA	0/12 (0%)		1/11 (9.1%)
HYPOTHYROIDISM	1/12 (8.3%)		0/11 (0%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/12 (8.3%)		0/11 (0%)
BACK PAIN	0/12 (0%)		1/11 (9.1%)
COSTOCHONDRITIS	1/12 (8.3%)		0/11 (0%)
LIGAMENT SPRAIN	1/12 (8.3%)		0/11 (0%)
MUSCULOSKELETAL PAIN	0/12 (0%)		1/11 (9.1%)
MYALGIA	1/12 (8.3%)		0/11 (0%)
NECK PAIN	0/12 (0%)		1/11 (9.1%)
PAIN IN EXTREMITY	0/12 (0%)		1/11 (9.1%)
Nervous system disorders
HEADACHE	2/12 (16.7%)		1/11 (9.1%)
DIZZINESS	0/12 (0%)		1/11 (9.1%)
NEUROPATHY PERIPHERAL	1/12 (8.3%)		0/11 (0%)
Respiratory, thoracic and mediastinal disorders
BRONCHITIS VIRAL	0/12 (0%)		1/11 (9.1%)
COUGH	0/12 (0%)		1/11 (9.1%)
Vascular disorders
HOT FLUSH	1/12 (8.3%)		0/11 (0%)
HYPERTENSION	1/12 (8.3%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.